Career Development Aim: To develop into an independent, productive academician conducting translational research in the field of HIV pathogenesis. Career Development Methods: An individualized, mentored curriculum of peer and faculty interactions, formal didactics, and study development are proposed. Scientific Background: 15,000 people in the world will become infected with human immunodeficiency virus (HIV) today. Most of these infections will occur through sexual contact, and yet HIV within genital secretions is not as well characterized as that found in the blood. Genital tract compartmentalization has profound consequences on the development of drug resistance and the selection of HIV quasispecies for transmission. Research Aim: To characterize the genital tract as a separate compartment than from the blood secondary to different host cell selection immunologic responses and pharmacologic penetration. [unreadable] [unreadable] Research Methods: Male genital secretions are a complex mixture of secretions and cells. The amount of HIV within male genital secretions is highly variable. Sequestration of HIV within the genital tract will be explored by studying the role of the prostate, which is known to sequester both bacterial and fungal pathogens and is a source of seminal fluid. This will be investigated by examining the effect of prostate massage, which increases the amount of prostatic fluid in genital secretions, on the amount of cell-free and cell associated virus. Longitudinally collected paired samples of genital secretions and blood from subjects enrolled in the UCSD Acute and Early HIV Cohort will be examined. From these samples HIV RNA will be extracted and examined with clonal and consensus sequencing and length polymorphism detection of the HIV env and gag coding regions. Comparing the genetic diversity of HIV between the genital tract and blood and subsequent divergence will give a better idea of the type of compartmentalization that is occurring and what kind of virus is ultimately being transmitted. Using these same samples the appearance and disappearance of drug resistance will be tracked. This may shed light on the mechanism of drug resistance development and why so many new infections are occurring with drug resistant HIV. Significance: These studies are important to characterize the compartmentalization of HIV in the genital tract, and to understand factors affecting the transmission of HIV and treatment approaches to minimize drug resistance. [unreadable] [unreadable]